The broad, long-term goal of this project is to improve our understanding of the biological processes that contribute to the etiology and maintenance of excessive drinking and alcoholism in humans. The project focuses directly on variables influencing ethanol's hedonic (rewarding and aversive) effects. The central, organizing hypothesis of this. research is that. ethanol's hedonic effects are modulated by ethanol-induced hypothermia. Research completed during the previous project period has supported this hypothesis by showing that ethanol's aversive effects are weakened when ethanol hypothermia is reduced. The general experimental strategy proposed here involves examination of variables believed to influence ethanol's thermal and hedonic effects in three behavioral tasks using animals (rats, mice): taste conditioning, place conditioning, and operant oral self-administration of ethanol. Body temperature effects of ethanol will be monitored continuously using radio telemetry. Proposed experiments will address the central hypothesis from three directions. One series of experiments is intended to further characterize and extend our findings on temperature-dependent modulation of ethanol's hedonic effects. These experiments will examine effects of high and low ambient temperature, signalling stimuli , and rebound hyperthermia on ethanol hypothermia and behavioral measures of ethanol's positive and negative effects. A second series of experiments will address suggestions that effects of opiate agonists or antagonists on ethanol's hedonic properties are mediated by changes in ethanol hypothermia and that temperature-dependent alterations in ethanol's hedonic effects are mediated by changes in endogenous opioid activity. The first study in this series will parametrically examine effects of morphine and naloxone on ethanol hypothermia, while subsequent studies will examine ethanol-opioid system interactions in each of the behavioral tasks. The of experiments will study the genetic relationship between ethanol's thermal and hedonic effects using genetically heterogeneous mice, mice selectively-bred for sensitivity or resistance to ethanol hypothermia (HOT and COLD), as well as a panel of 15 inbred mouse strains. These studies will assess effects of altered ambient temperature on ethanol hypothermia and behavior in taste and place conditioning tasks. Overall, this research will further characterize the relationship between ethanol's thermal and hedonic effects and begin to shed light on possible neurochemical mechanisms. Positive findings would strongly encourage further study of the role played by ethanol's thermal effects in the etiology of excessive drinking and alcoholism. An important implication of this hypothesis is that individual differences in sensitivity to ethanol's thermal effects due either to genotype, experience, or environmental conditions may be critically involved in the development of excessive drinking and dependence.